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Prior vaccination promotes early activation of memory T cells and enhances immune responses during SARS-CoV-2 breakthrough infection
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of vaccinated individuals is increasingly common but rarely results in severe disease, likely due to the enhanced potency and accelerated kinetics of memory immune responses. However, there have been few opportunities to rigorously study early recall responses during human viral infection. To better understand human immune memory and identify potential mediators of lasting vaccine efficacy, we used high-dimensional flow cytometry and SARS-CoV-2 antigen probes to examine immune responses in longitudinal samples from vaccinated individuals infected during the Omicron wave. These studies revealed heightened spike-specific responses during infection of vaccinated compared to unvaccinated individuals. Spike-specific cluster of differentiation (CD)4 T cells and plasmablasts expanded and CD8 T cells were robustly activated during the first week. In contrast, memory B cell activation, neutralizing antibody production and primary responses to nonspike antigens occurred during the second week. Collectively, these data demonstrate the functionality of vaccine-primed immune memory and highlight memory T cells as rapid responders during SARS-CoV-2 infection.
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“Recent findings have shown that vaccine-induced CD8+ T cell responses are important for long-term immunity and should also be considered as a correlate of protection29,30.”
From An Omicron-specific, self-amplifying mRNA booster vaccine for COVID-19: a phase 2/3 randomized trial (2024) · cites this paper as [30]
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Metadata
- Authors
- Painter, M. M., Johnston, T. S., Lundgreen, K. A., Santos, J. J. S., Qin, J. S., Goel, R. R., Apostolidis, S. A., Mathew, D., Fulmer, B., Williams, J. C., McKeague, M. L., Pattekar, A., Goode, A., Nasta, S., Baxter, A. E., Giles, J. R., Skelly, A. N., Felley, L. E., McLaughlin, M., Weaver, J., BioBank, P. M., Ritchie, M. D., Feldman, M. D., Weaver, J., Naseer, N., Poindexter, A., Brock, A., Hu-Sain, K., Ko, Y.-A., Livingstone, M., Vadivieso, F., Kloter, A., DerOhannessian, S., Tran, T., Morrel, L., Haubein, N., Dunn, J., Verma, A., Morse, C., Risman, M., Judy, R., Verma, S. S., Bradford, Y., Dudek, S., Drivas, T., Kuthuru, O., Dougherty, J., Adamski, S., Long, S., Kee, M., Clendenin, C., da Silva Antunes, R., Grifoni, A., Weiskopf, D., Sette, A., Huang, A. C., Rader, D. J., Hensley, S. E., Bates, P., Greenplate, A. R., & Wherry, E. J.
- Affiliations
- University of Pennsylvania (US)
- National Institutes of Health (US)
- Parker Institute for Cancer Immunotherapy (US)
- University of Michigan (US)
- University of Pennsylvania Health System (US)
- La Jolla Institute for Immunology (US)
- Corresponding author
- Wherry, E. John
- ORCID
- Painter, Mark M.
- Johnston, Timothy S.
- Lundgreen, Kendall A.
- Santos, Jefferson J. S.
- Qin, Juliana S.
- Goel, Rishi R.
- Apostolidis, Sokratis A.
- Mathew, Divij
- Fulmer, Bria
- Williams, Justine C.
- McKeague, Michelle L.
- Pattekar, Ajinkya
- Baxter, Amy E.
- Giles, Josephine R.
- Skelly, Ashwin N.
- Ritchie, Marylyn D.
- Feldman, Michael D.
- Kuthuru, Oliva
- Dougherty, Jeanette
- Adamski, Sharon
- Long, Sherea
- Clendenin, Cynthia
- da Silva Antunes, Ricardo
- Grifoni, Alba
- Weiskopf, Daniela
- Sette, Alessandro
- Huang, Alexander C.
- Rader, Daniel J.
- Hensley, Scott E.
- Bates, Paul
- Greenplate, Allison R.
- Wherry, E. John
- Venue
- Nature Immunology
- Published
- 2023-09-21
- Volume
- 24
- Issue
- 10
- Pages
- 1711-1724
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W4386923860
- Cited by
- 106
- References
- 70
- Citations by year
- 2026: 22 · 2025: 32 · 2024: 40 · 2023: 10
- FWCI
- 21.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Health & Human Services | National Institutes of Health (AI082630, AI108545, AI155577, AI149680, U19AI082630, 75N9301900065, AI152236)
- Parker Foundation
- U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (UL1TR001878)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- SARS-CoV-2, breakthrough infection, COVID-19 vaccination, memory T cells, CD4+ T cells, CD8+ T cells, plasmablasts, memory B cells, Omicron variant, recall immune response, neutralizing antibodies
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, Memory B Cells, Memory T Cells, Breakthrough Infections, Adult, Antibodies, Viral, Female, Humans, Immunologic Memory, Lymphocyte Activation, Male, Middle Aged, Vaccination, CD8-Positive T-Lymphocytes, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus
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